2-Phenoxy-1,4-naphthoquinones: From a Multitarget Antitrypanosomal to a Potential Antitumor Profile

摘要: A small library of 2-phenoxy-1,4-naphthoquinone and 2-phenoxy-1,4-anthraquinone derivatives was initially developed to optimize the antitrypanosomatid profile multitarget hit compound B6 (1). The whole series evaluated against three most important human trypanosomatid pathogens (Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani), two compounds (14 21) showed good activity, despite a concomitant mammalian cytotoxicity. Furthermore, subset also inhibited glycolytic TbGAPDH enzyme in vitro. In light these results aware antitumor properties quinones, anticancer potential some selected investigated. Intriguingly, tested displayed while being less toxic noncancerous cells. observed cytotoxic potency ascribed mechanism action accounting for hGAPDH inhibition mitochondrial toxicity. Overall, development further derivatives, able finely modulate multiple pathways cancer or parasite cell metabolism, might lead more effective treatments devastating diseases.